Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002027216 | SCV002308962 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-03-17 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. This variant has not been reported in the literature in individuals with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 1963 of the ATM protein (p.Asp1963His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. |
| Ambry Genetics | RCV002352754 | SCV002649492 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-19 | criteria provided, single submitter | clinical testing | The p.D1963H variant (also known as c.5887G>C), located in coding exon 38 of the ATM gene, results from a G to C substitution at nucleotide position 5887. The aspartic acid at codon 1963 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |